Glioblastoma Multiforme (GBM) is the most common malignant brain tumor of adults and is among the most lethal of all cancers. Analysis of large clinical databases demonstrates clinical prognostic groups of glioblastoma patients, suggesting considerable biological heterogeneity(Curran W J, 1993 J Natl Cancer Ins 85:704-710;Scott C B, 1998 Int J Radiat Oncol Biol Phys. 1998 Jan. 1;40(1):51-5. Recent data suggest that morphologically indistinguishable glioblastomas have distinct classes of causal oncogene activation and downstream signaling pathway deregulation that may affect survival and response to therapy (Mischel P S, 2003 Cancer Biol Ther 2(3)242-7; Mischel P S, 2003 Brain Pathol 13(1)52-61; Mischel P S, 2003 Oncogene 22(15)2361-73; Mischel, 2003 #3120; Shai, 2003 #3161; Chakravarti, 2001 Clin Cancer Res (1)2387-2395. Deregulation of the PI3K/Akt pathway signaling, which promotes malignant transformation, tumor progression and radiation-resistance in pre-clinical models, is common in glioblastomas (Choe, 2003 Cancer Res 63:2742-2746; Chakravarti, 2003 #3229; Chakravarti, 2004 Oncogene 23(45)7494-506; J Clin Oncol 22(10)1926-33; Int J Radiat Oncol Biol Phys 58(3)927-31).
It is an object of the present invention, therefore, to identify biomarkers that have prognostic value for GBM and to develop assays useful for identifying patients that may be suitable for targeted therapies.